Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma
Abstract
:1. Introduction
2. Results and Discussion
2.1. Bioactivity-Guided Fractionation of the Ethyl Acetate Extract of Aspergillus chevalieri
2.2. Structure Elucidation
2.3. Genome Sequencing
2.4. Cytotoxicity and Cell Cycle Analyses in the Pancreatic Ductal Adenocarcinoma Cell Line PANC-1
3. Materials and Methods
3.1. General Compound Spectroscopic Analysis and Purification Procedures
3.2. Fungal Material
3.3. Fermentation, Extraction, and Isolation
3.4. Crystallographic Analysis of Compound 2
3.5. DNA Isolation and Genome Sequencing
3.6. Cell Culture and Cytotoxic Activity
3.7. Cell Cycle Analysis
3.8. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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No. | δC, Type | δH (Mult, J in Hz) | HMBC (from H to C) |
---|---|---|---|
2 | 144.7, C | ||
3 | 102.8, C | ||
3a | 126.6, C | ||
4 | 116.6, CH | 6.93, d (1.5) | 3, 6, 7a, 21 |
5 | 134.5, C | ||
6 | 123.8, CH | 6.74, d (1.5) | 4, 7a, 26 |
7 | 123.5, C | ||
7a | 132.9, C | ||
8 | 113.2, CH | 7.23, s | 2, 3a, 10 |
9 | 124.0, C | ||
10 | 160.4, C | ||
12 | 51.8, CH | 4.27, q (6.9) | 10, 13, 20 |
13 | 165.5, C | ||
15 | 39.4, C | ||
16 | 144.6, CH | 6.05, dd (17.4, 10.5) | 2, 15, 18, 19 |
17 | 112.7, CH2 | 5.14, d (10.5) | 15, 16 |
5.12, d (17.4) | |||
18 | 27.6, CH3 | 1.51, s | 2, 15, 16, 19 |
19 | 27.5, CH3 | 1.50, s | 2, 15, 16, 18 |
20 | 21.1, CH3 | 1.60, d (6.9) | 12, 13 |
21 | 36.3, CH2 | 2.85, d (15.0) | 7, 7a, 28 |
2.94, dd (15.0, 8.7) | |||
22 | 78.2, CH | 3.80, d (8.7) | 7, 26, 28, 29, 30 |
23 | 77.8, C | ||
24 | 20.5, CH3 | 1.28, s | 27, 28, 30 |
25 | 18.5, CH3 | 1.23, s | 27, 28, 29 |
26 | 34.6, CH2 | 3.38, m | 4, 5, 6, 22, 23 |
27 | 124.3, CH | 5.35, m | 24, 25 |
28 | 132.0, C | ||
29 | 25.9, CH3 | 1.72, s | 22, 23, 25 |
30 | 18.0, CH3 | 1.71, s | 22, 23, 24 |
1-NH | 10.21, s | 2, 3, 3a, 7a | |
11-NH | 6.34, br s | 10, 13 | |
14-NH | 7.47, br s | 10, 12, 13 | |
23-OCH3 | 49.4, OCH3 | 3.28, s | 28 |
Contig No. | Length (bp) | Coverage (x-Fold) | Secondary Metabolite Regions |
---|---|---|---|
2 | 4,649,651 | 4036 | NRPS-like; fungal-RiPP-like; terpene; NI-siderophore |
187 | 3,079,001 | 4045 | T1PKS |
123 | 2,864,395 | 4042 | NRPS; T1PKS |
260 | 1,732,854 | 4039 | NRPS |
71 | 1,589,188 | 4047 | NRPS; fungal-RiPP-like; terpene |
284 | 1,488,407 | 4039 | NRPS-like |
328 | 1,357,148 | 4052 | no secondary metabolite region found |
315 | 1,177,976 | 4057 | no secondary metabolite region found |
149 | 21,917 | 3994 | Terpenoid cyclases/Protein prenyltransferases |
Compound | IC50 (±SD) [µM] |
---|---|
PANC-1 | |
1 | 25.8 ± 1.3 |
4 | 23.4 ± 1.8 |
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El-Kashef, D.H.; Obidake, D.D.; Schiedlauske, K.; Deipenbrock, A.; Scharf, S.; Wang, H.; Naumann, D.; Friedrich, D.; Miljanovic, S.; Haj Hassani Sohi, T.; et al. Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma. Mar. Drugs 2024, 22, 5. https://doi.org/10.3390/md22010005
El-Kashef DH, Obidake DD, Schiedlauske K, Deipenbrock A, Scharf S, Wang H, Naumann D, Friedrich D, Miljanovic S, Haj Hassani Sohi T, et al. Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma. Marine Drugs. 2024; 22(1):5. https://doi.org/10.3390/md22010005
Chicago/Turabian StyleEl-Kashef, Dina H., Deborah D. Obidake, Katja Schiedlauske, Alina Deipenbrock, Sebastian Scharf, Hao Wang, Daniela Naumann, Daniel Friedrich, Simone Miljanovic, Takin Haj Hassani Sohi, and et al. 2024. "Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma" Marine Drugs 22, no. 1: 5. https://doi.org/10.3390/md22010005